Mixed lineage leukemias(MLLs) are an evolutionarily conserved trithorax
family of human genes that play critical roles in HOXgene regulation and
embryonic development.MLL1is well known to be rearranged in myeloid
and lymphoid leukemias in children and adults. There are several MLL
family proteins such as MLL1, MLL2, MLL3, MLL4, MLL5, Set1A and
Set1B, and each possesses histone H3 lysine 4 (H3K4)-specific methyltrans-ferase activity and has critical roles in gene activation and epigenetics.
RNA processing is an essential process in eukaryotic cells, creating different RNA species
from one and the same gene. RNA processing occurs on nearly all kinds of RNAs, including
mRNA that codes for proteins, ribosomal RNA, tRNA, snRNAs, and RNA. RNA
processing usually occurs co-transcriptionally, and many factors are recruited by the RNA
polymerase itself. This stimulates RNA processing by enhancing the correct assembly of
factors as the RNA is being produced. Some factors, such as splice factors and cleavage
factors for rRNA, are also recruited by the growing RNA-chain.
Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles. The metabolome represents the collection of all metabolites in a biological cell, tissue, organ or organism, which are the end products of cellular processes.
Proteins are the driving force for all cellular processes. They regulate several cellular
events through binding to different partners in the cell. They are capable of binding to
other proteins, peptides, DNA, and also RNA. These interactions are essential in the
regulation of cell fates and could be important in drugs development. For example
RNA interacting proteins regulate gene expression through the binding to different
mRNAs. These mRNAs could be involved in important cellular processes such as cell
survival or apoptosis.
We have developed a simple reporter assay useful for detection and analysis
of mutations and agents influencing mRNA biogenesis in a gene length-dependent manner. We have shown that two transcription units sharing the
same promoter, terminator and open reading frame, but differing in the
length of their 3¢-untranslated regions, are differentially influenced by muta-
In trypanosomatids, the regulation of gene expression occurs mainly at the
post-transcriptional level. Previous studies have revealed nontranslated
mRNA in theTrypanosoma cruzicytoplasm. Previously, we have identified
and cloned the TcDHH1 protein, a DEAD box RNA helicase. It has been
reported that Dhh1 is involved in multiple RNA-related processes in vari-ous eukaryotes.
A number of antibiotics have been reported to disturb the
decoding process in prokaryotic translation and to inhibit
the function of various natural ribozymes. We investigated
the eect of several antibiotics on in vitro splicing of a
eukaryotic nuclear pre-mRNA (b-globin). Of the eight
antibiotics studied, erythromycin, Cl-tetracycline and
streptomycinwere identi®ed as splicing inhibitors in nuclear
HeLa cell extract. TheKi values were 160, 180 and 230lM,
Besides splicing, eukaryotic cells perform several other kinds of processing on their RNAs. Messenger RNAs are subject to two kinds of processing, known as capping and polyadenylation. In capping, a special blocking nucleotide (a cap) is added to the 59-end of a pre-mRNA. In polyadenylation, a string of AMPs (poly[A]) is added to the 39-end of the pre-mRNA. These steps are essential for the proper function of mRNAs and will be topics in this chapter.
Chapter 15 - RNA Processing II: Capping and Polyadenylation. Besides splicing, eukaryotic cells perform several other kinds of processing on their RNAs. Messenger RNAs are subject to two kinds of processing, known as capping and polyadenylation. In capping, a special blocking nucleotide (a cap) is added to the 59-end of a pre-mRNA. In polyadenylation, a string of AMPs (poly[A]) is added to the 39-end of the pre-mRNA. These steps are essential for the proper function of mRNAs and will be topics in this chapter.
RNA turnover and processing have now been demonstrated to be
important steps that directly affect protein synthesis and the cell’s ability to
survive in nature. However, the analysis of mRNA decay and polyadenylation
in Escherichia coli has long been considered technically difficult. The
development over the past 15 years of methods for the isolation and characterization
of both mRNA and polyadenylated species has made the study of
these important pathways of RNA metabolism more straightforward
(Arraiano et al., 1988; O’Hara et al., 1995; Mohanty and Kushner, 1999)....
MicroRNAs (miRNAs) are small, noncoding RNAs of 18–25 nucleotides
that are generally believed to either block the translation or induce the deg-radation of target mRNA. miRNAs have been shown to play fundamental
roles in diverse biological and pathological processes, including cell prolif-eration, differentiation, apoptosis and carcinogenesis.
important regulators of biological processes in animals
and plants. MiRNAs regulate gene expression at
the posttranscriptional level by binding to mRNAs and
either inhibit translation or modify the stability of the
mRNA. Due to the important biological role of miRNAs
it is of great interest to study their expression level in
the cells. Furthermore, miRNAs have been associated
with cancer and other diseases  and miRNA expression
can help in the diagnosis and prognostic of human
Flow of genetic information. Multiple extracellular signals activate intracellular signal cascades that result in altered regulation of gene expression through the interaction of transcription factors with regulatory regions of genes. RNA polymerase transcribes DNA into RNA that is processed to mRNA by excision of intronic sequences. The mRNA is translated into a polypeptide chain to form the mature protein after undergoing posttranslational processing.
The RNA degradosome is built on the C-terminal half of ribonuclease E
(RNase E) which shows high sequence variation, even amongst closely
related species. This is intriguing given its central role in RNA processing
and mRNA decay. Previously, we have identified RhlB (ATP-dependent
DEAD-box RNA helicase)-binding
PUF proteins regulate both stability and translation through sequence-spe-cific binding to the 3¢ UTR of target mRNA transcripts. Binding is medi-ated by a conserved PUF domain, which contains eight repeats of
approximately 36 amino acids each. Found in all eukaryotes, they have
been related to several developmental processes.
Polypyrimidine tract-binding protein (PTB) is a widely expressed RNA-binding protein with multiple roles in RNA processing, including the splic-ing of alternative exons, mRNA stability, mRNA localization, and internal
ribosome entry site-dependent translation. Although it has been reported
that increased expression of PTB is correlated with cancer cell growth, the
role of PTB in mammalian development is still unclear.
Poly(A)-specific ribonuclease (PARN) specifically catalyzes the degradation
of the poly(A) tails of single-stranded mRNAs in a highly processive mode.
PARN participates in diverse and important intracellular processes by act-ing as a regulator of mRNA stability and translational efficiency. In this
article, the equilibrium unfolding of PARN was studied using both guani-dine hydrochloride and urea as chemical denaturants.
The synthesis of ribosomal proteins (RPs) has long been known to be a
process strongly linked to the growth status of the cell. In vertebrates, this
coordination is dependent on RP mRNA translational efficiency, which
changes according to physiological circumstances.
In eukaryotes, two heteroheptameric Sm-like (Lsm) complexes that differ
by a single subunit localize to different cellular compartments and have dis-tinct functions in RNA metabolism. The cytoplasmic Lsm1–7p complex
promotes mRNA decapping and localizes to processing bodies, whereas the
Lsm2–8p complex takes part in a variety of nuclear RNA processing